Malignant rabbit fibroma virus (MV) infects and relicates in lymphocytes, is profoundly immunosuppressive, and causes disseminated tumors. Shope fibroma virus (SFV) is related to MV, but causes only local tumors and does not replicate in lymphocytes. We propose here to study the nature of the gene(s) in MV that determine its ability to infect and replicate in lymphocytes. Inserting into SFV the DNA from the "C" restriction fragment that results from BAM HI digestion of MV transfers to SFV the ability to replicate in lymphocytes and to suppress the immunologic function of these target lymphocytes. We propose to determine which gene(s) on this fragment is responsible for this function, the nature of the product of this gene, and the mechanism of action of the encoded protein. Host factors that may play a role in MV infection of lymphocytes will also be examined. The accomplishment of these goals will permit us to understand the genetic and molecular basis for the ability of lymphocytotrophic virus to ineect and replicate in lymphocytes, and perhaps provide us with greater understanding for the role of immunosuppression in the dissemination of tumors of viral origin.